Morphine disrupts macrophage functions even during HIV infection

John M. Barbaro, Matias Jaureguiberry-Bravo, Simone Sidoli, Joan W. Berman

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-associated neurocognitive impairment (HIV-NCI) is a debilitating comorbidity that reduces quality of life in 15–40% of people with HIV (PWH) taking antiretroviral therapy (ART). Opioid use has been shown to increase neurocognitive deficits in PWH. Monocyte-derived macrophages (MDMs) harbor HIV in the CNS even in PWH on ART. We hypothesized that morphine (MOR), a metabolite of heroin, further dysregulates functional processes in MDMs to increase neuropathogenesis. We found that, in uninfected and HIV-infected primary human MDMs, MOR activates these cells by increasing phagocytosis and up-regulating reactive oxygen species. Effects of MOR on phagocytosis were dependent on μ-opioid receptor activity and were mediated, in part, by inhibited lysosomal degradation of phagocytized substrates. All results persisted when cells were treated with both MOR and a commonly prescribed ART cocktail, suggesting minimal impact of ART during opioid exposure. We then performed mass spectrometry in HIV-infected MDMs treated with or without MOR to determine proteomic changes that suggest additional mechanisms by which opioids affect macrophage homeostasis. Using downstream pathway analyses, we found that MOR dysregulates ER quality control and extracellular matrix invasion. Our data indicate that MOR enhances inflammatory functions and impacts additional cellular processes in HIV-infected MDMs to potentially increases neuropathogenesis in PWH using opioids.

Original languageEnglish (US)
Pages (from-to)1317-1328
Number of pages12
JournalJournal of Leukocyte Biology
Volume112
Issue number5
DOIs
StatePublished - Nov 2022

Keywords

  • ER quality control
  • HIV-NCI
  • ROS
  • VEGFR2 signaling
  • antiretroviral therapy
  • myeloid cells
  • opioid receptors
  • opioids
  • phagocytosis
  • proteomics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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